The long-term objective of the proposed study is to reduce the risk of breast cancer (BCa) by immunizing control women against a cell-mediated immunity (CMI) determinant of preinvasive BCa. The immediate objectives are: a) correlating the risk of metastases with the degree of nuclear differentiation (nuclear grade, NG) of the primary BCa and skin window (SW) reactivity against autologous BCa tissue, b) correlating the risk of second primary BCa with SW reactivity against the first BCa and/or the gp55 component of the RIII-murine mammary tumor virus. These objectives are derived from prior observations by the Principal Investigator and associates on the prognostic significance of prospectively classified NG and SW reactivity: 1. NG is inversely correlated with the risk of early metastases from BCa; 2. SW reactivity against NG-characterized autologous BCa in inversely correlated with the risk of early metastases; 3. SW reactivity against autologous BCa is inversely correlated with the risk of a second invasive BCa within the subsequent four years; 4. the prognostically significant immunogen of BCa is characterized by a CMI determinant which is similar to one of gp 55; 5. this gp55-like CMI determinant is characteristically expressed during the preinvasive phase of mammary carcinogenesis; thus, SW reactivity to gp55 is inversely correlated with the risk of an invasive BCa within the subsequent four years. The proposed prospective study will determine whether these findings can be reproduced under the following conditions: 1. participation of BCa patients from different geographic areas; 2. morphologic classification of all primary BCa under coded conditions; 3. tests of SW reactivity against autologous BCa and gp55 at defined postoperative intervals, performed by different teams; 4. evaluation of SW test results under coded conditions; 5. collation and statistical evaluation of all data by a central registry at the NCI. Confirmation of the significance of the correlation of NG and SW reactivity with subsequent behavior of BCa would be important with regard to a) individualization of current therapy and b) development of immunoprophylaxis.